Investigation of Leptin and its receptor (LEPR) for single nucleotide polymorphisms in colorectal cancer: a case-control study involving 2,306 subjects

Abstract

Single nucleotide polymorphisms (SNPs) in the genes coding for leptin (LEP) and its receptor (LEPR) might regulate energy balance and be implicated in the development of colorectal cancer (CRC). In the present investigation, 1,003 CRC cases and 1,303 matched controls was compared. Five functional SNPs in LEP and LEPR genes were chosen to evaluate the correlation of these chosen SNPs with CRC susceptibility. We used the SNPscan^TM genotyping assay to genotype LEP and LEPR SNPs. A significantly decreased risk of CRC was found to be associated with the LEPR rs6588147 polymorphism (GA vs. GG: crude P=0.007 and GA/AA vs. GG: crude P=0.018). With adjustments for risk factors (e.g. age, gender, drinking, BMI and smoking), these associations were not changed. In subgroup analyses, the association of LEP rs2167270 with a decreased risk of CRC was found in the ≥61 years old subgroup. For LEPR rs1137100, the association of this SNP with an increased susceptibility of CRC was found in the BMI <24 kg/m² subgroup. In subgroup analyses for LEPR rs6588147, we identified that this locus also decreased the susceptibility of CRC in the male subgroup, <61 years old subgroup, never smoking subgroup and never drinking subgroup. For LEPR rs1137101, the relationship of this polymorphism with a decreased susceptibility to CRC was found in the never drinking subgroup. In summary, the present study highlights that LEPR rs6588147, rs1137101 and LEP rs2167270 may decrease the risk of CRC. However, LEPR rs1137100 is associated with susceptibility to CRC. Further case-control studies with larger sample sizes should be conducted to validate our findings.

Keywords: LEP/LEPR; colorectal cancer; polymorphisms; single nucleotide polymorphisms.

Figure 1

LEPR rs1137101 G>A SNPs, GG, AA, GA from top to bottom.

Figure 2

LEPR rs2167270 G>A SNPs, GG, AA, GA from top to bottom.

Figure 3

LEPR rs7799039 A>G SNPs, GG, AA, GA from top to bottom.

Figure 4

LEPR rs6588147 G>A SNPs, GG, AA, GA from top to bottom.

Figure 5

LEPR rs1137100 G>A SNPs, GG, AA, GA from top to bottom.

Figure 6

Using the SNPscanTM genotyping method to obtain the genotypes of LEP and LEPR SNPs. the sequencing results of each of the SNPs. *; number of miss cases in Cases =23, **; number of miss cases in Controls =3.